Postoperative neurological deficits are disabling and potentially lethal complications of cardiac surgery. Although embolization of gaseous and particulate matter has been observed during cardiopulmonary bypass, impaired cerebral perfusion during bypass contributes significantly to the severity of the deficit. In studies of canine hypothermic bypass, cerebral vascular resistance increased unexpectedly during rewarming by 260-380% over baseline so that cerebral blood flow failed to improve. Although cerebral oxygen extraction increased significantly, the cerebral metabolic rate for oxygen remained depressed after rewarming. The etiology and significance of this persistent increment in cerebral vascular resistance are not known but may predispose to neurological deficits postoperatively. Subsequent experimental studies show that cerebral hypoperfusion occurs with hypothermic but not normothermic bypass, indicating that cardiopulmonary bypass per se does not cause this defect. The proposed investigation will analyze in depth the factors governing defective cerebral perfusion and metabolism during rewarming in a canine model of cardiopulmonary bypass. The relationships among cerebral blood flow, vascular resistance, oxygen metabolism, and the electroencephalogram will be characterized under various conditions. Intracranial pressure will be measured directly and intracranial edema formation assessed by brain water content and specific gravity. Microembolization and ischemic damage will be assessed by postmortem retinal and cerebral histopathology. The marked increase in cerebral vascular resistance after rewarming on cardiopulmonary bypass may be due to a regional imbalance between vasodilator and vasoconstrictor influences. While tightly controlling all influential factors during bypass, four hypotheses will be tested during rewarming: 1) hyperglycemia decreases cerebral perfusion pressure and blood flow, 2) calcium channel blockade with nimodipine reduces cerebral vascular resistance and improves cerebral perfusion, 3) adenosine, infused directly into the cerebrospinal fluid space, increases cerebral blood flow more than acetylcholine and sodium nitroprusside indicating that hypothermic bypass impairs endothelially mediated relaxation of cerebral vascular smooth muscle, and 4) the increase in cerebral vascular resistance is dependent upon the duration of antecedent hypothermia and only partially resolves after 4 hours of normothermic pulsatile flow. Clinical studies of cardiopulmonary bypass are limited by the hemodynamic parameters which can be measured practically or ethically. Our canine model will establish guidelines to improve cerebral perfusion following hypothermic bypass.